Clinics (Sao Paulo, Brazil) · 2026
Early combination of terlipressin and norepinephrine in the treatment of patients with septic shock.
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Ding Zhenxing, Li Mingqing, Chen Yuanyuan
Аннотация
OBJECTIVES: This study set out to determine whether early use of Terlipressin (TP) as an adjunct to Norepinephrine (NE) could improve clinical outcomes in patients with septic shock.
MATERIAL AND METHODS: In this prospective, randomized trial, 104 patients with septic shock were assigned to three groups receiving TP at different NE thresholds: Low-dose (L, ≥ 0.25 μg/kg/min), Mid-dose (M, ≥ 0.5 μg/kg/min), and High-dose (H, ≥ 0.75 μg/kg/min). Primary outcomes included 28-day mortality and vasopressor-free days. Secondary outcomes encompassed hemodynamic parameters, organ function recovery, inflammatory markers, and adverse events.
RESULTS: No significant difference was observed in 28-day mortality among groups (L: 42.86 %, M: 47.06 %, H: 51.43 %; p = 0.328). However, the L group exhibited significantly more vasopressor-free days (defined as days alive and free of all vasopressor support for ≥ 24 consecutive hours within the first 7-days after randomization; median 4.2, IQR 2.1-5.3) than the M (3.1-days) and H groups (2.3-days; p < 0.01). Key secondary outcomes showed superior hemodynamic stabilization in the L group, with shorter time to target MAP (4.2 vs. 5.6-6.5 h, p < 0.05) and accelerated lactate clearance (p < 0.01). Organ function recovery was significantly enhanced in the L group, demonstrated by reduced CRRT duration (3.5 vs. 6.8-7.5 days, p < 0.001), improved renal and hepatic function, higher platelet counts (215 vs. 130-165 × 10⁹/L, p < 0.001), and more rapid inflammatory resolution (Procalcitonin and CRP reduction, all p < 0.05). Adverse events were significantly lower in the L group (p < 0.001).
CONCLUSIONS: Early low-dose TP adjunctive therapy reduces NE dependence, enhances hemodynamic stability, promotes multi-organ function recovery, and improves safety profile in septic shock, without significantly affecting 28-day mortality. These findings support its role as a beneficial adjunct vasopressor when initiated at lower NE doses.
MATERIAL AND METHODS: In this prospective, randomized trial, 104 patients with septic shock were assigned to three groups receiving TP at different NE thresholds: Low-dose (L, ≥ 0.25 μg/kg/min), Mid-dose (M, ≥ 0.5 μg/kg/min), and High-dose (H, ≥ 0.75 μg/kg/min). Primary outcomes included 28-day mortality and vasopressor-free days. Secondary outcomes encompassed hemodynamic parameters, organ function recovery, inflammatory markers, and adverse events.
RESULTS: No significant difference was observed in 28-day mortality among groups (L: 42.86 %, M: 47.06 %, H: 51.43 %; p = 0.328). However, the L group exhibited significantly more vasopressor-free days (defined as days alive and free of all vasopressor support for ≥ 24 consecutive hours within the first 7-days after randomization; median 4.2, IQR 2.1-5.3) than the M (3.1-days) and H groups (2.3-days; p < 0.01). Key secondary outcomes showed superior hemodynamic stabilization in the L group, with shorter time to target MAP (4.2 vs. 5.6-6.5 h, p < 0.05) and accelerated lactate clearance (p < 0.01). Organ function recovery was significantly enhanced in the L group, demonstrated by reduced CRRT duration (3.5 vs. 6.8-7.5 days, p < 0.001), improved renal and hepatic function, higher platelet counts (215 vs. 130-165 × 10⁹/L, p < 0.001), and more rapid inflammatory resolution (Procalcitonin and CRP reduction, all p < 0.05). Adverse events were significantly lower in the L group (p < 0.001).
CONCLUSIONS: Early low-dose TP adjunctive therapy reduces NE dependence, enhances hemodynamic stability, promotes multi-organ function recovery, and improves safety profile in septic shock, without significantly affecting 28-day mortality. These findings support its role as a beneficial adjunct vasopressor when initiated at lower NE doses.